The prognosis for patients with “masked” hypertension (MHT),¹ in which blood pressure is lower in clinical settings than during ambulatory monitoring, and for patients with “white-coat” hypertension (WCHT),² in which blood pressure is higher in clinical settings (casual blood pressure) but normal during ambulatory monitoring, has not been investigated in the general population. The objective of our longitudinal study was to compare the risk in patients with WCHT, MHT, sustained hypertension, and sustained normal blood pressure in a representative cohort of the general population in Japan.

Patients and methods
We obtained 24-hour ambulatory and casual blood pressure values on 1332 patients aged >= 40 years, which represented 67% of the total eligible population in Ohasama, Iwate Prefecture, Japan.³ Patients were classified into 4 groups on the basis of cut-off values for daytime ambulatory blood pressure (135/85 mm Hg) and casual blood pressure (140/90 mm Hg), derived from several guidelines^4-6: sustained normal blood pressure, WCHT, MHT, and sustained hypertension.

The ABPM-630 device (Nippon Colin, Komaki, Japan), a fully automatic monitoring instrument, was used to measure ambulatory blood pressure. Patients were asked to keep a diary of daily activities, including the times they awoke each morning and went to bed each night. Mean ambulatory daytime and nighttime blood pressures were computed. Technicians or nurses at nearby clinics took blood pressure measurements with the USM-700F device (UEDA Electronic Works, Tokyo, Japan) on seated patients after they had rested for 2 minutes. The mean value of the 2 readings was considered the casual blood pressure measurement.

Using the Cox proportional hazards regression model, we assessed the association between each blood pressure category and the risk of the primary outcome, which was the composite of cardiovascular mortality and stroke morbidity, and between each blood pressure category and the risk of the secondary outcomes, which were cardiovascular mortality and stroke morbidity individually. The associations were adjusted for sex, smoking status, use of antihypertensive medications, and a history of cardiovascular disease, hypercholesterolemia, or diabetes mellitus. The sustained normal blood pressure group was treated as the reference category. A value of P < .05 was considered to be statistically significant.

Results
As shown in the Table, compared with the other 3 groups, the 739 patients (53%) with sustained normal blood pressure had fewer risk factors. With regard to the proportion of men, age, and other risk factors, there were no differences between the 221 pa­tients (17%) in the MHT group and the 170 patients (13%) in the WCHT group. Compared with patients in the MHT and WCHT groups, the 202 patients (15%) in the sustained hypertension group had a higher percentage of men, older patients, patients with hypercholesterolemia, and patients who smoked.

There were 67 (5%) and 124 (9%) cardiovascular and noncardiovascular deaths, respectively, during a mean (SD) follow-up period of 10.2 (27) years; 112 patients experienced stroke, and there were 152 composite cardiovascular mortality and stroke morbidity events. As shown in Figure 1, patients with sustained normal blood pressure (treated as the reference group) had a markedly lower relative hazard (RH) for the composite events than the MHT and sustained hypertension groups; the RH for the WCHT group, however, was similar to the sustained normal blood pressure group. For risk of cardiovascular mortality and stroke morbidity, similar associations were shown.

As shown in Figure 2, the same associations occurred with patients categorized as low risk (no risk factors and no history of diabetes or cardiovascular disease), middle risk (1 or 2 risk factors and no history of diabetes or cardiovascular disease), and high risk (3 risk factors and a history of diabetes or cardiovascular disease). Risk factors included having smoked, having hypercholesterolemia, age > 55 years for men, and age > 65 years for women.

Discussion
The risks related to WCHT and MHT have never been shown before in a representative sample of the general population in a prospective study. Patients with MHT that is not detected by routine office blood pressure measurements appear to have stroke and death rates similar to that of patients with SHT, whereas patients with so-called WCHT appear to have no greater risk than people with normal blood pressure.

Almost 1 of 5 participants in this study had MHT, that is, their blood pressure appeared to be normal according to conventional blood pressure measurements in an office but it was high when measured by a 24-hour monitoring device. It is important for physicians and other health practitioners to recognize the possibility that conventional office blood pressure measurements may not reveal MHT. Otherwise, they may not suspect MHT if a patient develops cardiovascular disease despite good blood pressure control according to measurements taken in the office. If these patients are not identified and do not receive appropriate treatment, they could develop further organ damage or cardiovascular problems.

Ideally, every adult should be screened with an ambulatory blood pressure monitor at least once. If universal screening with 24-hour ambulatory monitoring is difficult, we recommend screening individuals who have an increased risk of cardiovascular disease because in our study, the absolute risk was extremely high in patients with MHT in the high-risk category (approximately 25% probability of death from cardiovascular disease or stroke during a 10-year period). Home blood pressure monitors can also be used to help identify patients because these devices have been reported to be superior to casual blood pressure measurements in predicting cardiovascular events^7,8 and are easier to use than ambulatory blood pressure monitors. Screening patients who have a high probability of having MHT, such as those with target organ damage despite having normal office blood pressure, those with relatively high office blood pressure, those who smoke, and those who drink, would also be an efficient method of asessment.^8-11

Individuals with WCHT might need antihypertensive treatment only if other factors place them at high risk for cardiovascular disease, because the absolute risk for WCHT patients in the high-risk group was at least as high as the risk for MHT and SHT patients with low risk. Several clinical trials that used blood pressure–lowering drugs and that included high-risk patients showed that the benefit of blood pressure–lowering treatment was also apparent in pa­tients with normal blood pressure.¹² Thus, treatment of WCHT patients in the high-risk group with blood pressure–lowering drugs would be useful in decreasing the risk of blood pressure–related cardiovascular diseases.¹²

Patients with WCHT should be carefully followed-up with ambulatory or home blood pressure measurements because their long-term prognosis has not been clarified. Using home blood pressure measurements, we also found that patients with WCHT were at high risk for developing true hypertension compared with true normotension over 8 years.¹³ Randomized, controlled trials and studies of other populations are needed to fully understand the risks and appropriate therapy for MHT and WCHT.

Conclusions
The results of our study showed that patients with WCHT had a 10-year composite risk of stroke morbidity and cardiovascular mortality similar to that of patients with sustained normal blood pressure. The risk for patients with MHT and sustained hypertension, however, was significantly increased compared with patients with sustained normal blood pressure. This shows that some patients at high or low risk may not be identified with standard blood pressure measurement.

Acknowledgments
The authors are grateful to the staff at the Iwate Prefectural Stroke Registry for their valuable support in the follow-up survey. This work was supported by Grants for Scientific Research (12877163, 13470085, 13671095, 15790293) from the Ministry of Ed­ucation, Culture, Sports, Science and Technology; by Health Science Research Grants on Health Services (13170201, 13072101, H12-Medical Care-002) and H15-Gan Yobou-039 from the Ministry of Health, Labour and Welfare, Japan; and by Research Grants from Junkanki-byo Itaku Kenkyu 11C-5 (1999 and 2000), the Japan Atherosclerosis Prevention Fund (2000 to 2003), Uehara Memorial Foundation (2002), Grant from Japan Cardiovascular Research Foundation (2002), and the Takeda Medical Research Foundation (2003).

References
1. Pickering TG, Davidson K, Gerin W, et al. Masked hypertension. Hypertension. 2002;40(6):795-796.

2. Pickering TG, James GD, Boddie C, et al. How common is white-coat hypertension. JAMA. 1988;259(2):225-228.

3. Ohkubo T, Imai Y, Tsuji I, et al. Prediction of mortality by ambulatory blood pres-sure monitoring versus screening blood pressure measurements: a pilot study in Ohasama. J Hypertens. 1997;15(4): 357-364.

4. Chobanian AV, Bakris GL, Black HR, et al. National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289(19): 2560-2572.

5. European Society of Hypertension-Eur­opean Society of Cardiology Guidelines Committee. 2003 European Society of Hypertension-European Society of Car­diology guidelines for the management of arterial hypertension. J Hypertens. 2003;21(6):1011-1053.

6. Japanese Society of Hypertension Guide­lines Subcommittee for the Management of Hypertension. Guidelines for the management of hypertension for general practitioners. Hypertens Res. 2001;24(6):613-634.

7. Ohkubo T, Imai Y, Tsuji I, et al. Home blood pressure measurement has a stronger predictive power for mortality than does screening blood pressure measurement: a population-based observation in Ohasama, Japan. J Hypertens. 1998;16(7):971-975.

8. Bobrie G, Chatellier G, Genes N, et al. Cardiovascular prognosis of “masked hypertension” detected by blood pressure self-measurement in elderly treated hypertensive patients. JAMA. 2004;291(11):1342-1349.

9. O’Brien E, Asmar R, Beilin L, et al; European Society of Hypertension Working Group on Blood Pressure Monitoring. European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement. J Hypertens. 2003;21(5):821-848.

10. Pickering TG, Hall JE, Appel LJ, et al; Subcommittee of Professional and Public Education of the American Heart As­sociation Council on High Blood Pressure Research. Recommendations for blood pressure measurement in humans and experimental animals: part 1: blood pressure measurement in humans: a statement for professionals from the Subcommittee of Professional and Public Education of the American Heart Association Council on High Blood Pressure Research. Hypertension. 2005;45(1):142-161.

11. Obara T, Ohkubo T, Funahashi J, et al. Isolated uncontrolled hypertension at home and in the office among treated hypertensive patients from the J-HOME study. J Hypertens. 2005;23(9): 16531660.

12. MacMahon S, Neal B, Rodgers A. Hypertension—time to move on. Lancet. 2005;365(9464):1108-1109.

13. Ugajin T, Hozawa A, Ohkubo T, et al. White-coat hypertension as a risk factor for the development of home hypertension: the Ohasama study. Arch Intern Med. 2005;165(13):1541-1546.

A more detailed discussion of this topic can be found in Ohkubo T, Kikuya M, Metoki H, et al. Prognosis of “masked” hypertension and “white-coat” hypertension detected by 24-h ambulatory blood pressure monitoring. J Am Coll Cardiol. 2005;46(3): 508-515.